We have investigated the association of single nucleotide polymorphisms with cerebral palsy in infants born very prematurely, using archived neonatal blood. Four genetic variants were associated with increased risk of cerebral palsy; the targeted genes have roles in inflammation, coagulation, or vasomotor regulation. A paper describing these results is in press. We are investigating the association of these genetic variants with features observed on neonatal cranial ultrasonography. We are now seeking to corroborate (or refute) and extend the initial findings in an investigation in the Laboratory of Molecular Technology, using additional biologic samples from California plus a large material, cases and controls, from a population-based registry of cerebral palsy in Australia, with the collaboration of Dr. Alastair MacLennan. Genotyping is also proceeding on DNA from buccal smears from the study of pediatric stroke with Dr. John Lynch. Dr. Lynch has a paper on adult stroke in press, and a paper on pediatric and perinatal stroke, from the NINDS Pediatric Stroke Study, is in preparation. In collaboration with Dr. Robert Yolken we are involved in a study of antibodies to selected bacterial and viral agents in archived neonatal blood of children with cerebral palsy or autism, and control children. With Dr. Phillip Nelson (NICHD) we have examined concentrations of total protein and of certain neurotrophins, neuropeptides, and cytokines in neonatal blood of children with Down syndrome or autism, and examining the developmental trajectory of these substances in the blood of very premature infants, term infants, and healthy adults recruited from the Blood Bank of NIH. Blood concentrations of brain derived neurotrophic factor increased with age, while values of interleukin-8 were highest in very premature infants and in term infants with Down syndrome, and CGRP concentrations were higher in control newborns than in healthy adults, suggesting some function of this neuropeptide in infancy. A manuscript describing these findings is in preparation.